Structures of a

Virus
A Tour to the nature’s deadliest weapon.
Recall:
What’s the difference
between virus and virion?
Virion are complete viral
particle that consist of a
genome with a protein coat or
with a external envelope at
time
Extracellular infective form of
a virus
VIRION
Gene delivery system  containing the
genome
So what does a virion function for?
 Protects the genome
 Protein aids in entry to host
 Replicate the genome  packaged in a
capsid
 What are the main structures
of a virion?
1. Genome
2. Capsid
3. Lipid envelope (may be present)
4. Protein occlusion bodies (for protection)
1. Viral genome
Virion contains a genome
May consist of one or more
nucleic acid
Can be RNA or DNA

During isolation how can one

identify if the virion contains
DNA or RNA?
 Testing for susceptibility on
Ribonuclease.
Classification of virion based on nucleic
acid

1. ds DNA  encode genes

same way as plants,
animals, bacteria
2. ss DNA  circovirus
3. ds RNA  typical for
fungal viruses
4. ss RNA  most plant
viruses
Virion genome can also be
classified as:
1. Linear
 with free 5’ and 3’
ends,
2. Circular
 covalently closed
Virion genome also
contains:

+
-
What is meant by these
signs on the genome?
• most of the nucleic acid strands are labelled (+) or (−).
• RNA+ or RNA -
• labelling is relative to the virus mRNA,  always
designated (+)
• nucleic acid strand that has the same sequence as
mRNA is labelled (+)
• and a nucleic acid strand that has the sequence
complementary to the mRNA is labelled (−).
Positive-sense
• Positive-sense (5' to 3') viral RNA signifies that a particular viral RNA sequence may
be directly translated into the desired viral proteins.
• Therefore, in positive-sense RNA viruses, the viral RNA genome can be considered
viral mRNA, and can be immediately translated by the host cell.

• Unlike negative-sense RNA, positive-sense RNA is of the same sense as mRNA.

• Some viruses (e.g., Coronaviridae) have positive-sense genomes that can act as
mRNA and be used directly to synthesize proteins without the help of a
complementary RNA intermediate.
• Because of this, these viruses do not need to have an RNA polymerase packaged into
the virion.
Negative-sense
• Negative-sense (3' to 5') viral RNA is complementary to the viral mRNA and thus from
it a positive-sense RNA must be produced by an RNA-dependent RNA
polymerase prior to translation.
• Negative-sense RNA (like DNA) has a nucleotide sequence complementary to
the mRNA that it encodes.
• Like DNA, this RNA cannot be translated into protein directly. Instead, it must first be
transcribed into a positive-sense RNA that acts as an mRNA.
• Some viruses (Influenza, for example) have negative-sense genomes and so must
carry an RNA polymerase inside the virion.
But…take a look at:
DNA in hepadnavirus virions
RNA in influenza virions

Some linear molecules

may be in a circular
conformation as a
result of base pairing
between
complementary
sequences at their ends
Virion span ranges of
genome size 1.2. Genome size
 Porcine circovirus (ssDNA)
 and hepatitis delta virus
(ssRNA) each have a
genome of about 1.7
kilobases (kb),
dsDNA genomes comprised
of over 1000 kilobase pairs
(kbp).
The maximum size of a virus
genome is subject to
constraints, which vary with
the genome category.
As the constraints are less
severe for dsDNA
 all of the large virus
genomes are composed of
dsDNA.
 The largest RNA genomes
known are those of some
coronaviruses, (33 kb of
ssRNA)

Largest virus genomes  the

mimivirus,  larger than
mycoplasmas.
1.3 Secondary and Tertiary Structures
Information carried by the viral genome:
1. Encode viral proteins
2. Encode untranslated RNA
3. Signals control of gene expression

SIGNALS are found on:

d.s.  within the nucleotide
s.s.  contained within structures formed by
intramolecular base pairing.
S.S. GENOME
s.s. DNA
Base pair through G-C
A- T hydrogen bonding

s.S RNA
weaker G–U bonds may form in
addition to G–C and A–U base
pairing.
 Intramolecular base pairing results
in regions of secondary structure
with stem- loops and bulges
ssRNAS

Formation of pseudoknots
may form

 Functions for genome

replication
 Internal ribosome entry site

Tertiary
structure

 Regions of secondary structure in single-stranded

nucleic acids are folded with specific shapes
 depicts the 5’ end of poliovirus RNA
 there is an internal ribosome entry site to which cell
proteins bind to initiate translation
Some pseudoknots have enzyme activity,
while others play a role in ribosomal
frameshifting.
What is ribosomal frameshifting?

• a second ORF in an mRNA involves ribosomal frameshifting

• a ribosome shifts into a different reading frame towards the end of ORF 1.
• It therefore does not recognize the ORF 1 stop codon,
• but continues along the mRNA, reading ORF 2
• to produce an elongated version of the ORF 1 protein
 Frameshifting occurs when the ribosome moving along the RNA
 encounters a frameshift signal (a specific sequence) followed by a secondary
structure, usually a pseudoknot.
1.4. Modification at the end
• genomes of some DNA viruses and many RNA viruses are modified at one or both
ends
• Some genomes have a covalently linked protein at the 5’ end.
• a vestige of a primer
• used for initiation of genome synthesis
RNA viral genome with one
or both ends modified

The 5’end may be linked to

a protein or a methylated
nucleotide cap

The 3’ end may be

polyadenylated or it may be
folded like a transfer RNA
Some genome RNAs have one or both of the modifications
occur in eukaryotic messenger RNAs (mRNAs):
a. a methylated nucleotide cap at the 5 end
b. a sequence of adenosine residues (a polyadenylate tail; poly(A) tail) at the 3’
end)
The genomes of many RNA
viruses function as mRNAs
(during infection)
 cap and a poly(A) tail on a
genome RNA may indicate
that the molecule is ready
to function as mRNA,
but neither structure is
essential for translation.
All the ssRNAs function as
mRNAs,
but not all have a cap and a
poly(A) tail.
In the case of plant viruses…

• genomes of some ssRNA plant viruses are base

paired
• and folded near their 3’ ends
• to form structures similar to transfer RNA.
• structures contain sequences that promote the
initiation of RNA synthesis.
 1.5 proteins non covalently associated
with virus genomes
• nucleic acids packaged in virions
have proteins bound to them non-
covalently
• encoded in two or more nucleic
acid molecules
• segmented genomes are much
more common amongst RNA
viruses than DNA viruses.
(influenza virus, ssRNA)
• package the segments in one
virion,
• Most dsRNA viruses, such as
members of the family Reoviridae
have segmented genomes.
possession of a segmented genome provides a virus with the
possibility of new gene combinations

and hence a potential for more rapid evolution

viruses with the segments packaged in separate virions

 A new cell becomes infected only if all genome segments

enter the cell, which means that at least one of each of the
virion categories must infect.
1.5 Repeated sequences
These sequences include:
• promoters,
• enhancers,
• origins of replication
• and other elements  involved in the
control of events in virus replication.
• linear virus genomes have
repeat sequences at the ends
(termini),
• in which case the sequences
are known as terminal repeats
• If the repeats are in the same
orientation they are known as
direct terminal repeats (DTRs),
• whereas if they are in the
opposite orientation they are
known as inverted terminal
repeats (ITRs).
• the sequences referred to
as ‘ITRs’ in single-stranded
nucleic acids are NOT
REPEATS
• But until the second strand
is synthesized during
replication.
• In the single-stranded
molecules the ‘ITRs’ are, in
fact, repeats of the
complementary sequences
• see ssDNA and ssRNA (−)
2. Viral Protein
As the size of the genome increases, so the number of protein
species tends to increase

FACT!
• tobacco mosaic virus contains only one protein species
• parvoviruses contain two to four protein species.
• herpes simplex virus 1 contains 39 protein species
• algal virus Paramecium bursaria Chlorella virus 1 contain 100
protein species
Proteins that are components of virions
are known as structural proteins
Functions:
• protection of the virus genome
• attachment of the virion to a host cell (for many viruses)
• fusion of the virion envelope to a cell membrane (for enveloped
viruses).
Other ROLES:
enzymes, e.g. protease, reverse transcriptase
• transcription factors
• primers for nucleic acid replication
• interference with the immune response of the host.
Can we classify virus based on protein?
• In a virion the virus genome is enclosed in a protein
coat, known as a capsid.
• the genome and the capsid constitute the virion,
• while for other viruses there are additional
components.
• may be an envelope at the surface of the virion,
in which case there may be:
a.protein between the envelope and the capsid,
b.an internal lipid membrane.
NOTE: A few viruses produce protein occlusion bodies
in which virions become embedded.
 Virus genomes removed from
their capsids are more
susceptible to inactivation, CAPSIDS
 major function of the capsid:
 the protection of the genome

Second major function:

“recognize and attach to a host cell
in which the virus can be replicated”

 capsid is the protein shell of a virus.

 consists of several oligomeric structural
subunits made
of protein called protomers.
 Observable 3-dimensional morphological
subunits, which may or may not
correspond to individual proteins, are
called capsomeres.
 Capsid encloses the genetic material of
the virus.
Protomer:
• a PROTOMER is the structural unit of an oligomeric protein.
• A PROTOMER can be a protein subunit or several different
subunits, that assemble in a defined stoichiometry to form
an oligomer.
• protomer is the smallest subset of different subunits that
form the oligomer.
• The PROTOMER usually arrange in cyclic symmetry to form
closed point group symmetries.
• Protomers are the main subunit in a viral capsid.
For many viruses the capsid and the genome that it
encloses constitute the virion.

For other viruses a lipid envelope

and sometimes another layer of protein, surrounds

this structure, which is referred to as a
nucleocapsid.
• Capsids are constructed
from many molecules of
one or a few species of
protein.
• The individual protein
molecules are
asymmetrical, but they
are organized to form
symmetrical structures.
• Some examples of
symmetrical structures
are shown beside:
 Symmetrical
 including a capsid,
 has the same appearance when it is
rotated through one or more angles,
 or when it is seen as a mirror image.

 capsid symmetry is either

helical or icosahedral.
 Capsids with
symmetrical symmetry
• The capsids of many ssRNA viruses
have helical symmetry;
• the RNA is coiled in the form of a
helix,
• many copies of the same protein
species are arranged around the
coil
(Figure 3.9(a), (b)).
• forms an elongated structure,
• may be a rigid rod if strong bonds
are present between the protein
molecules in successive turns of
the helix,
• or a flexible rod if these bonds are
weak.

The length of the capsid is determined by the

length of the nucleic acid
For many ssRNA viruses…
(such as measles and
influenza viruses)

the helical nucleic acid

coated with protein forms a
nucleocapsid, which is inside
an envelope.

The nucleocapsid may be

coiled or folded to form a
compact structure.
The virions of some plant viruses
that have helical symmetry (e.g.
tobacco mosaic virus)
• are hollow tubes;
• allows the entry of negative
stain,
• making the center of the
virion appear dark in electron
micrographs.
• The rod-shaped tobacco rattle
virus has a segmented
genome with two RNAs of
different sizes packaged in
separate virions
• resulting in two lengths of
virion.
 The virion of a
few DNA viruses,
such as the
filamentous
phages also have
helical symmetry
Capsids with icosahedral symmetry
What is an icosahedron?

An icosahedron is an object with:

• 20 faces, each an equilateral
triangle;
• 12 vertices, each formed where the
vertices of five triangles meet;
• 30 edges, at each of which the
sides of two triangles meet.
An icosahedron
has five-,
three-
and two-fold
axes of
rotational
symmetry
Capsids with icosahedral symmetry consist of :
• a shell built from protein molecules
• appear to have been arranged on scaffolding
in the form of an icosahedron.
• have less contact with the virus genome than
the capsid proteins of viruses with helical
symmetry.
To construct an icosahedron
from identical protein
molecules:
• the minimum number of
molecules required is three
per triangular face,
• giving a total of 60 for the
icosahedron (Figure 3.11(a)).
• The capsid of satellite
tobacco mosaic virus is
constructed in this way
(Figure 3.11(b)).
The capsids of many icosahedral
viruses are:
• composed of more than one
protein species.
• That of cowpea mosaic virus is
composed of two proteins (Figure
3.12):
• one is present as ‘pentamers’ at
the vertices of the icosahedron
(12×5 = 60 copies) and the other
is present as ‘hexamers’ on the
faces.
• ‘hexamer’ is composed of three
copies of a protein with two
domains.
• The arrangement is similar to
that of the panels on the surface
of the football.
 some capsids actually
have the shape of an
icosahedron,
 such as that of
Paramecium bursaria
Chlorella virus 1,
 which is 165 nm across
when measured along the
two- and three-fold axes
and 190 nm across when
measured along the five-
fold axes.
Capsids that have an
icosahedral shape have an
angular outline in electron
micrographs.
 An icosahedral shape is not an
inevitable outcome of
icosahedral symmetry;
 the football is constructed in
the form of icosahedral
symmetry,
 but the structure is spherical.
 Many small viruses that have
capsids with icosahedral
symmetry
 appear to be spherical, or
almost spherical,
 their virions are often described
as isometric, such as those of
densoviruses and foot and
mouth disease virus (Figure
3.13).
• Some capsids with icosahedral symmetry
are elongated.
• capsids of geminiviruses (plant viruses) are
formed from two incomplete icosahedra.
(above)
• Another plant virus, alfalfa mosaic virus,
has four sizes of virion; all are 19 nm
diameter,
• but three are elongated as a result of
insertions of a protein lattice between a
half icosahedral structure at each end of
the capsid. (beside)
Prolate
This is an icosahedron
elongated along the fivefold
axis
common arrangement to
heads of bacteriophages
Such a structure is
composed of a cylinder with
a cap at either end.
The cylinder is composed of
10 triangles.
 capsomeres
 The capsomere is a subunit of
the capsid, an outer covering of protein
that protects the genetic material of
a virus.
 Capsomeres self-assemble to form
the capsid.
 In this diagram of an Adenovirus, the
capsid molecules are clearly visible.
 Subunits called protomers aggregate
to form capsomeres.
 Various arrangements of capsomeres
are: 1) Icosahedral, 2) Helical, and 3)
Complex.
• The capsids of papillomaviruses are
constructed from 72 capsomeres,
• which are all identical,
• but the capsids of some viruses are
constructed from two types of
capsomere:
a. pentons, which are found at the
vertices of the icosahedron,
b. hexons, which make up the
remainder of the capsid. In these viruses
there are always 12 pentons (one at each
vertex),
 but the number of hexons varies; for
example, the capsids of herpesviruses
and adenoviruses contain 150 and 240
hexons, respectively.
 Capsid vertices
• icosahedral viruses have a structure
such as a knob, projection or fibre at
each of the 12 vertices of the capsid.
• For example, the virions of some
phages (e.g. G4; Figure 3.13)
• have projections, while the adenovirus
virion has a fibre, (larger image)
• with a knob attached, at each of the 12
pentons
• structures at the capsid vertices are
composed of distinct proteins that are
involved in attachment of the virion to
its host cell
• and in delivery of the virus genome into
the cell.
 Tailed bacteriophage
• The majority of the known phages
are constructed in the form of a
tail attached to a head,
• contains the virus genome.
• All of these phages have dsDNA
genomes.
• The head has icosahedral
symmetry and may be isometric
as in phage lambda (λ),
• or elongated as in phage T4.
• The tail, which is attached to one
of the vertices of the head via a
connector,
• may be long as in phage λ, or
short as in phage T7.
• may contain specialized structures
such as fibres and/or a baseplate.
• Some of the tailed phages have been
objects of intensive study and a lot of
the detail of their structures has been
uncovered.
• One such phage is T7
• Inside the head of phage T7 is a
cylindrical structure (the internal
core) around which the DNA is wound.
• The connector has a wider region
inserted into one of the vertices of the
head
• and a narrower region to which the
tail is attached.
• The tail is very short and tapers from
the connector to the tip; attached to
the tail are six tail fibres.
 Conical and rod-shaped capsids
• HIV-1 and baculoviruses have capsids
that are conical and rod shaped,
respectively
• Inside each capsid is a copy of the virus
genome coated in a highly basic
protein.
• Both of these viruses have enveloped
virions
 VIRION MEMBRANES
• Many viruses have a lipid
membrane component.
• In most of these viruses the
membrane is at the virion surface
• and is associated with one or
more species of virus protein.
• This lipid–protein structure is
known as an envelope
• and it encloses the nucleocapsid
(nucleic acid plus capsid).
• The virions of most enveloped
viruses, such as herpesviruses,
are spherical or roughly spherical,
but other shapes exist (Figure
3.19).
• Some viruses have a membrane
located not at the virion surface,
but within the capsid.
Envelope virion
Facts on viral envelopes:
• Many viruses (e.g. influenza and many animal viruses) have viral
envelopes covering their protective protein capsids.
• The envelopes typically are derived from portions of the host cell
membranes (phospholipids and proteins), but include some viral
glycoproteins.
• Functionally, viral envelopes are essential to entry into host cells.
• They may help viruses avoid the host immune system.
• Glycoproteins on the surface of the envelope serve to identify
and bind to receptor sites on the host's membrane.
• The viral envelope then fuses with the host's membrane,
allowing the capsid and viral genome to enter and infect the
host.
• Associated with the membranes of
an enveloped virus are one or more
species of protein.
• Most of these proteins are integral
membrane proteins and most are O-
and/or N-glycosylated.
• Many of the glycoproteins in virion
envelopes are present as multimers.
• The envelope of influenza A virus for
example, contains two glycoprotein
species: a haemagglutinin present as
trimers
• and a neuraminidase present as
tetramers.
• There is also a third protein species
(M2) that is not glycosylated.
• Some envelope proteins
span the membrane only
once
• but some, such as those of
hepatitis B virus span the
membrane several times.
• The polypeptide chain is
highly hydrophobic at each
membrane anchor.
• Some surface glycoproteins of
enveloped viruses perform the
function of fusing the virion
membrane to a cell membrane
during the infection process
• These fusion proteins have an
additional hydrophobic region
• plays a major role in the fusion
process.
• Many enveloped viruses, including
influenza viruses and retroviruses
• have a layer of protein between the
envelope and the nucleocapsid.
• This protein is often called a matrix
protein.
• In some viruses, however, such as
yellow fever virus,  such layer and
the nucleocapsid interacts directly
with the internal tails of the integral
membrane protein molecules.
 Membrane lipids
• Most virion membranes are
derived from host cell membranes
that undergo modification before
incorporation into virions.
• For example, the HIV-1 envelope
is derived from the plasma
membrane of the host cell
• but the virus envelope contains
more cholesterol and
sphingomyelin,
• and less phosphatidylcholine and
phosphatidylinositol.
Occlusion bodies
• Some viruses provide added protection to the virions while outside their hosts by occluding them
in protein crystals.
• These occlusion bodies, as they are known, are produced by many of the viruses that infect
invertebrates, including most baculoviruses.
• There are two major types of occlusion body in which baculoviruses embed their rod-shaped
virions;
• the granuloviruses form small granular occlusion bodies, generally with a single virion in each
• the nucleopolyhedroviruses form large occlusion bodies with many virions in each
Cell molecules
The incorporation of cell lipids into virions has already been
discussed.
Other cell molecules that become incorporated into virions include
the following.
• Transfer RNA molecules. These are present in the virions of
retroviruses.
• Proteins. When a virion is assembled some cell protein may be
incorporated. There are reports of HIV-1 incorporating several cell
proteins, including cyclophilin A in association with the capsid and
human leukocyte antigens in the envelope.
• Polyamines. Spermidine and other polyamines have been reported in
a variety of viruses.
Cations, such as Na+,K +, Zn 2+ and Mg2+ have also been reported as
components of virions. One likely role for polyamines and cations is
the neutralization of negative charges on the virus genome.
To be passed next week:

Does the difference on viral genome affects infectivity

or rate of infectivity of viruses?
• 1 whole paper, hand written
• outline important points
Explain by citing helpful literatures, and sample virus
or disease.